The combination of high-throughput methods of molecular biology
with advanced mathematical and computational techniques
has propelled the emergent field of systems biology into a position
of prominence. Unthinkable a decade ago, it has become possible
to screen and analyze the expression of entire genomes, simultaneously
assess large numbers of proteins and their prevalence, and
characterize in detail the metabolic state of a cell population.
Although very important, the focus on comprehensive networks of
biological components is only one side of systems biology. Complementing
large-scale assessments, and sometimes at the risk of
being forgotten, are more subtle analyses that rationalize the
design and functioning of biological modules in exquisite detail.
This intricate side of systems biology aims at identifying the
specific roles of processes and signals in smaller, fully regulated
systems by computing what would happen if these signals were
lacking or organized in a different fashion. We exemplify this type
of approach with a detailed analysis of the regulation of glucose
utilization in Lactococcus lactis. This organism is exposed to alternating
periods of glucose availability and starvation. During starvation,
it accumulates an intermediate of glycolysis, which allows
it to take up glucose immediately upon availability. This notable
accumulation poses a nontrivial control task that is solved with an
unusual, yet ingeniously designed and timed feedforward activation
system. The elucidation of this control system required highprecision,
dynamic in vivo metabolite data, combined with methods
of nonlinear systems analysis, and may serve as a paradigm for
multidisciplinary approaches to fine-scaled systems biology.